Investigating fundamental properties and clinical applications of the optoretinogram

摘要 这项资助将用于研究视网膜光图（ORG）-一种实验性的，对人类感光细胞的全光学分析 功能-及其在细胞水平揭示功能障碍的潜力。ORG是基于自适应光学光学 相干断层扫描（AO OCT），其是产生活体人类视网膜的3D图像的唯一现有方式 细胞分辨率。它利用了我们的新观察，即光刺激会导致大脑中的微观变形。 活体光感受器外节（OS），沿着OCT对组织变形的敏感性要小得多 比成像源的波长更长。目的1研究ORG测量视杆细胞功能的能力， 锥体，通过测量正常受试者的反应和表征信号对刺激信号变化的敏感性， LUS能量，以及影响这种灵敏度的因素，如响应的空间和时间变化，计算 因素和光子噪声。目的2探讨光刺激引起的OS变形的机制。我们将 严格确定变形饱和时的光照水平，多次闪光的效果，以及 信号对视网膜偏心率的依赖性，所有这些都提供了有关生物化学的有价值的信息。 导致观察到的变形的过程。目的3将ORG应用于充分表征的视网膜疾病， 确定其是否能够检测患有已知缺陷的光感受器中的病理性功能障碍。 反过来，充分表征的缺陷提供了自然实验，这些实验可能揭示生物化学和生物群系的缺陷。 所观察到的光刺激诱发的OS变形的机械决定因素。

Abstract This grant will investigate the optoretinogram (ORG)–an experimental, all optical assay of human photoreceptor function–and its potential to reveal dysfunction at the cellular level. The ORG is based on adaptive optics optical coherence tomography (AO­OCT), which is the only existing way to produce 3D images of the living human retina with cellular resolution. It leverage our novel observation that light stimuli cause microscopic deformations in the living photoreceptor outer segment (OS), along with OCT’s sensitivity to deformations in the tissue much smaller than the wavelength of the imaging source. Aim 1 investigates the ORG’s ability to measure function in rods and cones, by measuring responses in normal subjects and characterizing the signal’s sensitivity to changes in stimu­ lus energy, and factors affecting this sensitivity, such as spatial and temporal variance in response, computational factors, and photon noise. Aim 2 investigates the mechanisms underlying light­evoked OS deformation. We will rigorously determine the light levels at which the deformations are saturated, the effect of multiple flashes, and the signal’s dependence on retinal eccentricity, all of which provide valuable information about the biochemical processes causing the observed deformations. Aim 3 applies the ORG to well­characterized retinal disease, to determine whether it is able to detect pathological dysfunction in photoreceptors suffering from known deficits. Well­characterized deficits, in turn, offer natural experiments which may shed light on the biochemical and biome­ chanical determinants of the observed light­evoked deformations in the OS.